The major goals of this proposal are to crystallize and determine the X-ray structures of nucleotide systems, particularly ribo- and deoxyribo-oligonucleotides, both in their free state and in complexation with metals and drugs. Excellent crystals of the dinucleoside monophosphate CpA has been grown and complete data set has been collected and the structure analysis is in progress. The structure analysis is posing a challenge because there are at least four independent CpA molecules in the unit cell. Crystalization of a number of other di- and tetra-nucleotides are being carried out to further unravel the stereochemical principles governing the folding of the polynucleotide backbone, the base-pairing schemes and the nature of the solvation scheme. Conformational energy calculations are in progress in conjunction with the X-ray studies to provide a broader basis of our understanding of principles of nucleic acid structure, stability and function.